Process for the preparation of optically active beta-(p-hydroxyphenyl)-isopropylmethylamines



Patented Feb. 7, 1939 UNITED STATES PATENT OFFICE PROCESS FOR THE.PREPARATION OF OPTI- CALLY ACTIVE 5- (D-HYDROXYPHENYL)ISOPROPYLMETHYLAMINES Jersey City, N. J.

No Drawing. Application July 6, 1937, Serial No. 152,272. In GermanyApril 1'7, 1937 4 Claims.

The present invention relates to optically active ,3 (p hydroxyphenyl)isopropylmethylamines and a process for their preparation.

It is known that the racemic fl-(p-hydroxyphenyl) -isopropylmethylamineis physiologically active and is said to exert similar efiects toephedrine and its salts.

According to this invention it has been found that the optically activeB-(p-hydroxyphenyD- isopropylmethylamines obtained by treating opticallyactive 5 (p methoxyphenyl) -isopropylmethylamines with strong mineralacids at elevated temperatures exert therapeutic actions, which differadvantageously from those of the racemic compound.

Since optically active bases are frequently racemised or even partiallydecomposed by the action of strong mineral acids in the hot, it was byno means to be expected that the activefi-(phydroxyphenyl)-isopropylmethylamines could be obtained,particularly in very good yields, by treating the correspondingderivatives, methylated at the OH group, with strong acids. Thus it wasto be expected that on eliminating the methoxy group of the opticallyactive B-(pmethoxyphenyl) -isopropylmethylamines the bases would'beracemised.

Strong mineral acids, particularly strong hydrobromic acid, and alsohydrochloric acid and the like are used for eliminating the methoxygroup.

Examples 1. 20 gms. of d-fi-(p-methoxyphenyl) -isopropylmethylamine(obtained by resolving the racemic base with optically active acids, forexample optically active tartaric acid) are refluxed for about half anhour with 100 cos. of 48% hydrobromic acid. The reaction is completed assoon as the evolution of methyl bromide has ceased. The excesshydrobromic acid is distilled off under reduced pressure and the residueis taken up in a small quantity of water and precipitated with ammonia.An. approximately quantitative yield of d-p- (p-hydroxyphenyl)isopropylmethylamine in a pleasing crystalline form of melting point 131to 132 C. is obtained. The sulphate of the base in 4% aqueous solutionshows a specific rotation of 2. 20 gins. of l-fi-(p-methoxyphenyl)-isopropylmethylamine (obtained by resolving the racemic base withoptically active acid) are heated for one hour to 130 C. in a closedvessel with strong hydrochloric acid. The reaction mixture is worked upinto l-B-(p-hydroxyphenyl) -isopropylmethylamine as described inExample 1. Yield, melting point and specific rotation as in Example 1(with correspondingly reversed sign).

What we claim is 1. A process for the preparation of optically active [3(p-hydroxyphenyl) isopropylmethylamines, which consists in treatingoptically active {3 (p methoxyphenyl) isopropylmethylamines with astrong mineral acid heated at least to its boiling point.

2. A process for the preparation of optically active 5 (p hydroxyphenyl)-isopropylmethylamines, which consists in treating optically active 3 (pmethoxyphenyl) isopropylmethylamines with strong hydrobromic acid.

3. The chemical compounds optically active 5- (p-hydroxyphenyl)isopropylmethylamines of the group consisting of d-B-(p-hydroxyphenyD-isopropylmethylamine and l-p-(p-hydroxyphenyl) -isopropylmethylamine.

4. A process for the preparation of optically active 5 (p hydroxyphenyl)-isopropylmethylamines which consists in demethylating optically activefi- (p-methoxyphenyl) -isopropylmethyla; mines with a strong hydrohalicacid heated at least to its boiling point.

GUSTAV HILDEBRANDT. CARL FREESE.

